Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes

Maria Loredana Marcovecchio; Marco Colombo; Raymond Neil Dalton; Paul M McKeigue; Paul Benitez-Aguirre; Fergus J Cameron; Scott T Chiesa; Jennifer J Couper; Maria E Craig; Denis Daneman; Elizabeth A Davis; John E Deanfield; Kim C Donaghue; Timothy W Jones; Farid H Mahmud; Sally M Marshall; Andrew Neil; Helen M Colhoun; David B Dunger; AdDIT and the SDRNT1BIO Investigators

doi:10.1111/pedi.13095

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes

Pediatr Diabetes. 2020 Nov;21(7):1322-1332. doi: 10.1111/pedi.13095. Epub 2020 Aug 17.

Authors

Maria Loredana Marcovecchio¹, Marco Colombo², Raymond Neil Dalton³, Paul M McKeigue², Paul Benitez-Aguirre⁴, Fergus J Cameron⁵, Scott T Chiesa⁶, Jennifer J Couper⁷, Maria E Craig⁴, Denis Daneman⁸, Elizabeth A Davis⁹, John E Deanfield⁶, Kim C Donaghue⁴, Timothy W Jones⁹, Farid H Mahmud⁸, Sally M Marshall¹⁰, Andrew Neil¹¹, Helen M Colhoun¹², David B Dunger^{1

13}; AdDIT and the SDRNT1BIO Investigators

Affiliations

¹ Department of Paediatrics, University of Cambridge, Cambridge, UK.
² Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
³ Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
⁴ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, University of Sydney, Sydney, Australia.
⁵ Department of Paediatrics, University of Melbourne, Melbourne, Australia.
⁶ Institute of Cardiovascular Science, University College London, London, UK.
⁷ Departments of Endocrinology and Diabetes and Medical Imaging, Women's and Children's Hospital, Adelaide, Australia.
⁸ Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
⁹ Telethon Kids Institute, University of Western Australia, Perth, Australia.
¹⁰ Institute of Cellular Medicine (Diabetes), Faculty of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
¹¹ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
¹² Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
¹³ Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.

PMID: 32783254
DOI: 10.1111/pedi.13095

Abstract

Objectives: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D.

Methods: Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m² /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource.

Results: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10^-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10^-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10^-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10^-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10^-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10^-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10^-4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR.

Conclusions: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.

Keywords: GFR; adolescents; biomarkers; complications; kidney disease.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Age Factors
Biomarkers / blood
Child
Cohort Studies
Cystatin C / blood
Diabetes Mellitus, Type 1 / blood*
Diabetes Mellitus, Type 1 / complications*
Diabetic Nephropathies / blood*
Diabetic Nephropathies / diagnosis
Diabetic Nephropathies / etiology*
Fibroblast Growth Factor-23
Fibroblast Growth Factors / blood
Glomerular Filtration Rate
Humans
Middle Aged
Osteopontin / blood
Trefoil Factor-3 / blood
Young Adult
beta 2-Microglobulin / blood

Substances

B2M protein, human
Biomarkers
CST3 protein, human
Cystatin C
FGF23 protein, human
SPP1 protein, human
TFF3 protein, human
Trefoil Factor-3
beta 2-Microglobulin
Osteopontin
Fibroblast Growth Factors
Fibroblast Growth Factor-23

Abstract

Publication types

MeSH terms

Substances

Grants and funding